Description: (From the applicant's abstract) About 30 to 40 percent of all human proteins are expected to be integral membrane proteins. Although the sequences of all genes coding for these proteins will be known in the very near future, the three-dimensional structures of only a few of them have been solved. Structure prediction from sequences may be simpler for membrane proteins than for soluble proteins because the ordered fluid structure of the lipid bilayer constrains the folding of membrane proteins. The major limitation of this approach is that many of the relevant fundamental forces that govern membrane protein folding are not yet known. The goal of this project is to study the structure and folding of membrane proteins by using the outer membrane protein A (OmpA) of E. coli as a model. Specifically, the structure of the transmembrane domain of this channel protein will be solved by NMR spectroscopy. Elementary lipid-protein and protein-protein interactions will be determined that direct the folding of this and, by extension, other membrane proteins. How different lipids modulate folding and to what extent the C-terminal domain contributes to the folding of OmpA will be investigated. Finally, the role of a candidate periplasmic chaperone protein will be examined. Since folding of membrane proteins is not an established field, an important component of the proposed research is to continue to develop new methods that are suitable for the characterization of intermediates of membrane protein folding.